Interconnections within the tumor microenvironment: extracellular vesicles as critical players of metabolic reprogramming in tumor cells

Metabolic reprogramming is an intrinsic characteristic of cancer, contributing to its establishment and progression, survival, high proliferation rates, and increased migratory and invasive potential; tumor cells establish an intimate relationship with the surrounding microenvironment, where sustained communication allows the stromal fraction of the tumor microenvironment (TME) to supply energetic substrates and facilitate the biosynthesis of macromolecules, thereby promoting tumor progression. In this context, extracellular vesicles (EVs) emerge as potential communication vehicles, carrying inside content reflecting the cellular environment of origin and thus modulating the phenotype of recipient cells. The potential of EVs as modulators in the TME has been highlighted and is now consensual; however, most available articles have focused on revealing the effect of EVs in modulating tumor phenotypes and signaling pathways in tumor cells. Regarding the metabolic modulation sustained by EVs, studies have demonstrated the role of cancer cells’ EVs as modulators of surrounding cells, like immune cells, fibroblasts, and adipocytes. Therefore, this review aims to: i. highlight the most recent studies evaluating the role of cellular vesicles released by those cells within the microenvironment in the metabolic reprogramming of cancer cells; ii. compile scientific evidence proposing how EVs could modulate the metabolic profile of tumor stem cells and lymphocytes, particularly given the lack of studies focused on such approaches; and iii. highlight possible effects of vesicles, as the metabolic modulation induced by these vesicles could have anticancer potential.